Cross-over study of pharmacokinetics and haematological toxicity of 4'-epi-doxorubicin and doxorubicin in cancer patients.

Eight cancer patients were given 4'-epi-DX and DX (70 mg/m2) by i.v. route at three-week intervals according to a randomized cross-over design. Blood samples were drawn at different intervals of time after each drug administration and plasma levels of the unchanged drugs and of their main metabolites were determined by HPLC. 4'-epi-DX gave plasma levels constantly lower than those observed after DX; the pharmacokinetic study showed that 4'-epi-DX was eliminated from the body more rapidly (t1/2 30 hours as compared with 43 hours). The 13-dihydroderivatives of both drugs behaved in much the same way as the unchanged drugs; in fact the AUC values were lower for 13-OH 4'-epi-DX than for 13-OH DX. The cross-over design gave statistical confirmation of the lower haematological toxicity of 4'-epi-DX in comparison to DX. The reduced toxicity of 4'-epi-DX with respect to DX may be related to its pharmacokinetic behaviour.